The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver
The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver
复制标题
mPlrp2 和 mClps 基因参与小鼠肝脏中视黄酯的水解
DOI：
10.1194/jlr.m010082
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发表时间：
2011-05-01
影响因子：
6.5
通讯作者：
Zhang, Jianfa
中科院分区：
文献类型：
--
作者：
Pang, Wenqiang;Zhang, Ying;Zhang, Jianfa
视黄酸酯是储存在肝脏中的维生素A的主要化学形式，可以输送到周围组织，转化为具有生物活性的形式。潜在参与催化视黄酸酯水解酶的肝脏基因的功能和调控尚不清楚。在这里，我们发现了两个脂肪水解酶基因，胰腺相关蛋白2(MPlrp2)和前磷脂酶(MClps)，它们是在小鼠胰腺中特异表达的，与S-腺苷甲硫氨酸(ADOMet)和S-腺苷同型半胱氨酸(ADOHcy)的比率有关。光照不足或给予5‘-AMP可使ADO-Met/ADO-Hcy比值升高，并诱导mPlrp2和mClps在肝脏中的表达，该作用可被全反式维甲酸阻断。饲喂无维生素A饮食的小鼠表现出肝脏mPlrp2和mClps表达的激活，这与mPlrp2和mClps启动子附近的组蛋白H3K4残基甲基化增加有关。甲基酶抑制剂甲硫腺苷抑制肝脏mPlrp2和mClps的表达，显著降低这些小鼠的血浆视黄醇水平。活化的肝星状细胞(HSC)-T6细胞特异性表达mClps和mPlrp2。用短发夹状RNA(ShRNA)抑制mClps基因的表达可减少HSC-T6细胞中视黄酸酯的水解率。这些数据表明mPlrp2和mClps的条件性表达与小鼠肝脏视黄酸酯的水解性有关。MPlrp2和mClps基因参与了小鼠肝脏中视黄酸酯的水解。J.Lipid Res.2011年。52：934-941。
Retinyl esters are the major chemical forms of vitamin A stored in the liver, and can be delivered to peripheral tissues for conversion into biologically active forms. The function and regulation of the hepatic genes that are potentially involved in catalyzing the hydrolysis of retinyl esters remain unclear. Here we show that two lipid hydrolytic genes, pancreatic-related protein 2 (mPlrp2) and procolipase (mClps), expressed specifically in the mouse pancreas, are associated with the ratio of S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). Light illumination deficiency or administration of 5'-AMP elevated the ratio of AdoMet to AdoHcy and induced the expression in the liver of mPlrp2 and mClps, which was blocked by all-trans retinoic acid. Mice fed a vitamin A-free diet exhibited increased activation of hepatic mPlrp2 and mClps expression, which was associated with increased methylation of histone H3K4 residues located near the mPlrp2 and mClps promoters. Inhibition of hepatic mPlrp2 and mClps expression by a methylase inhibitor, methylthioadenosine, markedly decreased plasma retinol levels in these mice. The activated hepatic stellate cell (HSC)-T6 cell line specifically expressed mClps and mPlrp2. Inhibition of mClps gene expressions by short hairpin RNA (shRNA) decreased hydrolysis of retinyl esters in the HSC-T6 cell line.jlr These data suggest that the conditional expression of mPlrp2 and mClps is involved in the hydrolysis of retinyl esters in the mouse liver.-Pang, W., Y. Zhang, S. Wang, A. Jia, W. Dong, C. Cai, Z. Hua, and J. Zhang. The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver. J. Lipid Res. 2011. 52: 934-941.